[Frontiers in Bioscience 16, 2402-2415, June 1, 2011]

WT1/EGR1-mediated control of STIM1 expression and function in cancer cells

Michael F. Ritchie, Yandong Zhou, Jonathan Soboloff

Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140


1. Abstract
2. Introduction
2.1. Bcl2-mediated control of ER Ca2+ content in cancer cells
2.2. TRP cation channel function in cancer cells
2.3. Molecular Mechanisms of Ca2+ entry
2.4. The zinc finger transcription factors WT1 and EGR1
3. WT1 and EGR1: Oncogenes/tumor suppressors regulating Ca2+ homeostasis
3.1. WT1 as a negative regulator of STIM1 expression in Wilms Tumor
3.2. WT1, EGR1 and STIM1 in breast cancer
3.3. WT1, EGR1 and Ca2+ signaling in Acute Myeloid Leukemia
3.4. EGR1 and STIM1 expression in Glioblastoma
3.5. EGR1-mediated control of SOCe in prostate cancer
3.6. WT1/EGR1 and ovarian carcinoma
4. Summary and perspective
5. Acknowledgements
6. References


There have been numerous publications linking Ca2+ signaling and cancer, however, a clear explanation for this link has remained elusive. We recently identified the oncogenes/tumor suppressors Wilms Tumor Suppressor 1 (WT1) and Early Growth Response 1 (EGR1) as regulators of the expression of STIM1, an essential regulator of Ca2+ entry in non-excitable cells. The current review focuses on the literature defining both differential Ca2+ signaling and WT1/EGR1 expression patterns in 5 specific cancer subtypes: Acute Myeloid Leukemia, Wilms Tumor, breast cancer, glioblastoma and prostate cancer. For each tumor-type, we have assessed how specific changes in WT1 and EGR1 expression might contribute to aberrant Ca2+ homeostasis as well as the therapeutic potential of these observations.